HIF-2α as a prognostic marker for breast cancer progression and patient survival
Open accessAbstract
Malignant cells show increased invasion potency in vitro and in vivo. This process is considered to be mediated by matrix-metalloproteases (MMPs). Hypoxia-inducible factor-2α (HIF-2α) may upregulate MMP-2 expression; however, little is known about the correlation between HIF-2α and MMP-2 expressions in breast cancer. The current study investigated this correlation immunohistochemically according to various clinical and pathological features in 102 paraffin-embedded archival tissue block specimens from patients with breast cancer. HIF-2α and MMP-2 expression was detected in 60.8% (62/102) and 65.7% (67/102) of tumor samples, respectively. HIF-2α expression was significantly correlated with tumor size (P = 0.019), lymph node involvement (P = 0.035), and metastasis (P = 0.035). MMP-2 expression was significantly associated with lymph node involvement (P = 0.043) and metastasis (P = 0.003). Univariate analyses revealed that HIF-2α (P = 0.001) and MMP-2 (P = 0.000) expressions were significantly associated with a poorer survival rate, as well as tumor size, lymph node invasion, and distant metastasis. Multivariate analysis revealed that HIF-2α (P = 0.003) and the T-stage (P = 0.000) were independent prognostic factors of overall survival. Spearman correlation analysis revealed that HIF-2α and MMP-2 expressions were significantly correlated (r = 0.990; P = 0.041). These results suggest that high HIF- 2α expression is associated with poor overall survival in patients with breast cancer, indicating that HIF-2α could be a valuable marker of breast cancer progression.
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HIF-2 expression in primary tumors is associated with distant metastasis in patients with small cell lung and breast cancers.
“HIF-2 expression in primary tumors is also associated with distant metastasis in patients with small cell lung and breast cancers”
From Hypoxic control of metastasis (2016) · cites this paper as [40]
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Cites
Gorres, K. L., & Raines, R. T. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409231003627991 · Cited by 611 · see citing works
Singh, B., Fleury, C., Jalalvand, F., & Riesbeck, K. (2012) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2012.00340.x · Cited by 302 · see citing works
Sivridis, E., Giatromanolaki, A., Gatter, K. C., Harris, A. L., Koukourakis, M. I., & for the Tumor and Angiogenesis Research Group (2002) · Cancer · doi:10.1002/cncr.10774 · Cited by 218 · see citing works
Xue, X., Taylor, M. J., Anderson, E. R., Hao, C., Qu, A., Greenson, J. K., Zimmermann, E. M., Gonzalez, F. J., & Shah, Y. M. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3836 · Cited by 146 · see citing works
Hypoxia induces the activation of human hepatic stellate cells LX‐2 through TGF‐β signaling pathway
Shi, Y., Fong, C., Zhang, Q., Cheung, P., Tzang, C., Wu, R. S. S., & Yang, M. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.12.010 · Cited by 87 · see citing works
VEGF, HIF-1α Expression and MVD as an Angiogenic Network in Familial Breast Cancer
Saponaro, C., Malfettone, A., Ranieri, G., Danza, K., Simone, G., Paradiso, A., & Mangia, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053070 · Cited by 79 · see citing works
Matrix metalloproteinase 9/gelatinase B is required for neural crest cell migration
Ornan, E. M., Kosonovsky, J., Bar, A., Roth, L. E., Fraggi-Rankis, V., Simsa-Maziel, S., Kohl, A., & Sela‐Donenfeld, D. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.01.028 · Cited by 76 · see citing works
Horiuchi, A., Hayashi, T., Kikuchi, N., Hayashi, A., Fuseya, C., Shiozawa, T., & Konishi, I. (2012) · International Journal of Cancer · doi:10.1002/ijc.27448 · Cited by 69 · see citing works
Zhu, G., Tang, Y., Li, L., Zheng, M. H., Jiang, J. D., Li, X., Chen, S.-X., & Liang, X. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1408 · Cited by 66 · see citing works
He, C., Sun, X., Qiao, H., Jiang, X., Wang, D., Jin, X., Dong, X., Wang, J., Jiang, H., & Sun, X. (2011) · Cancer Science · doi:10.1111/j.1349-7006.2011.02177.x · Cited by 63 · see citing works
Pawlus, M. R., Wang, L., Ware, K., & Hu, C. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00724-12 · Cited by 63 · see citing works
HIF-1α and HIF-2α correlate with migration and invasion in gastric cancer
Wang, Y., Li, Z., Zhang, H., Jin, H., Sun, L. J., Dong, H., Xu, M., Zhao, P., Zhang, B., Wang, J., et al. (2010) · Cancer Biology & Therapy · doi:10.4161/cbt.10.4.12441 · Cited by 57 · see citing works
HIF-1α activation mediates resistance to anti-angiogenic therapy in neuroblastoma xenografts
Hartwich, J. E., Orr, W. S., Ng, C. Y., Spence, Y., Morton, C. L., & Davidoff, A. M. (2013) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2012.10.016 · Cited by 51 · see citing works
Wu, X.-H., Qian, C., & Yuan, K. (2011) · PubMed · Cited by 47 · see citing works
Kuo, W., Shih, C., Lin, C., Cheng, W.-E., Chen, S., Chen, W., & Lee, Y.-L. (2011) · Translational research · doi:10.1016/j.trsl.2011.09.003 · Cited by 40 · see citing works
Ali Osman, K. A. Y. A., Günel, N., Beneklı, M., Akyurek, N., Büyükberber, S., Tatli, H., Coskun, U., Yıldız, R., Yaman, E., & Ozturk, B. (2012) · PubMed · Cited by 39 · see citing works
Bougatef, F., Ménashi, S., Khayati, F., Naïmi, B., Porcher, R., Podgorniak, M.-P., Millot, G., Janin, A., Calvo, F. M., Lebbé, C., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012265 · Cited by 37 · see citing works
Hypoxia-Inducible Factor-2α (HIF-2α) Induces Angiogenesis in Breast Carcinomas
Giatromanolaki, A. N., Sivridis, E., Fiska, A., & Koukourakis, M. I. (2006) · Applied immunohistochemistry & molecular morphology · doi:10.1097/01.pai.0000145182.98577.10 · Cited by 35 · see citing works
Chen, C., Ma, Q., Ma, X., Liu, Z., & Liu, X. (2011) · Annals of Surgical Oncology · doi:10.1245/s10434-011-1587-5 · Cited by 34 · see citing works
The Role of Hypoxia-Inducible Factors in Oxygen Sensing by the Carotid Body
Semenza, G. L., & Prabhakar, N. R. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-4584-1_1 · Cited by 31 · see citing works
Prognostic Impacts of Hypoxic Markers in Soft Tissue Sarcoma
Smeland, E., Kilvaer, T. K., Sørbye, S. W., Valkov, A., Andersen, S., Bremnes, R. M., Busund, L., & Dønnem, T. (2012) · Sarcoma · doi:10.1155/2012/541650 · Cited by 27 · see citing works
Márton, I., Knežević, F., Ramić, S., Milošević, M., & Tomas, D. (2012) · PubMed · Cited by 27 · see citing works
Lu, L. S., Chen, L., Wx, D., Li, K., & Jj, W. (2012) · PubMed · Cited by 26 · see citing works
Fu, W., Wang, Y., Jin, Z., Wang, H., Cheng, W., Zhou, H., Yin, P., & Peng, W. (2012) · Renal Failure · doi:10.3109/0886022x.2012.723775 · Cited by 21 · see citing works
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- HIF-2α and breast carcinoma ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (2): 2817-2826 (2014)
Cited by
Sorted by citations
Rankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340 · see citing works
Deepak, K. G. K., Vempati, R. K., Nagaraju, G. P., Dasari, V. R., Nagini, S., Rao, D. N., & Malla, R. R. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104683 · Cited by 618 · see citing works
Hypoxia signaling in human health and diseases: implications and prospects for therapeutics
Luo, Z., Tian, M., Yang, G., Tan, Q., Chen, Y., Li, G., Zhang, Q., Li, Y., Wan, P., & Wu, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01080-1 · Cited by 499 · see citing works
Hypoxia: Signaling the Metastatic Cascade
Rankin, E. B., Nam, J.-M., & Giaccia, A. J. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.05.006 · Cited by 240 · see citing works
LDH-A regulates the tumor microenvironment via HIF-signaling and modulates the immune response
Serganova, I. S., Cohen, I., Vemuri, K., Shindo, M., Maeda, M., Mane, M. M., Moroz, E., Khanin, R., Satagopan, J. M., Koutcher, J. A., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0203965 · Cited by 118 · see citing works
Hypoxia and Bone Metastatic Disease
Johnson, R. W., Sowder, M. E., & Giaccia, A. J. (2017) · Current Osteoporosis Reports · doi:10.1007/s11914-017-0378-8 · Cited by 85 · see citing works
Moreno Roig, E., Yaromina, A., Houben, R., Groot, A. J., Dubois, L., & Vooijs, M. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00224 · Cited by 60 · see citing works
Shah, T. K., Krishnamachary, B., Wildes, F. B., Mironchik, Y., Kakkad, S. M., Jacob, D., Artemov, D., & Bhujwalla, Z. M. (2015) · Oncotarget · doi:10.18632/oncotarget.4612 · Cited by 33 · see citing works
The tumor promoting roles of HSP60 and HIF2α in gastric cancer cells
Tong, W., Tong, G., Kong, H., & Liu, Y. (2016) · Tumor Biology · doi:10.1007/s13277-015-4783-2 · Cited by 29 · see citing works
Hypoxia‐Inducible Factor‐2α Signaling in the Skeletal System
Mendoza, S. V., Genetos, D. C., & Yellowley, C. E. (2023) · JBMR Plus · doi:10.1002/jbm4.10733 · Cited by 22 · see citing works
Luo, D., Liu, H., Lin, D., Lian, K., & Ren, H. (2018) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-18-0881 · Cited by 17 · see citing works
Duchnowska, R., for the Central and East European Oncology Group (CEEOG), Wysocki, P. J., Korski, K., Czartoryska-Arłukowicz, B., Niwińska, A., Orlikowska, M., Radecka, B. S., Studziński, M., Demlová, R., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6375 · Cited by 8 · see citing works
Polymorphisms in HIFs and breast cancer sutarsceptibility in Chinese women: a case–control study
Shan, C., Zheng, Y., Wang, M., Lin, S., Tian, T., Deng, Y., Xu, P., Hao, Q., Wu, Y., Yang, T., et al. (2018) · Bioscience Reports · doi:10.1042/bsr20180950 · Cited by 5 · see citing works
Ray, S. K., & Mukherjee, S. (2022) · Current Molecular Medicine · doi:10.2174/1566524022666220513124853 · Cited by 5 · see citing works
Signaling Pathways Underlying Bone Metastasis: Hypoxia Signaling in Bone Metastasis and Beyond
Devignes, C.-S., Aslan, Y., & Provot, S. (2018) · Current Molecular Biology Reports · doi:10.1007/s40610-018-0090-1 · Cited by 3 · see citing works
The implied dysregulated RKIP-hypoxia axis in cancer and immune evasion: Clinical implications
McWhorter, R., Chouaı̈b, S., & Bonavida, B. (2025) · Drug Resistance Updates · doi:10.1016/j.drup.2025.101328 · Cited by 2 · see citing works
Prominent Prognostic Factors in Aggressive Breast Cancer: A Review
Nejati‐Koshki, K., Aval, S. F., Alivand, M. R., Akbarzadeh, A., & Arabzadeh, A. (2021) · International Journal of Cancer Management · doi:10.5812/ijcm.109015 · Cited by 2 · see citing works
Hypoxia-inducible Factors: Molecular Basis and Clinical Implications
Assi, M. H. (2023) · Mustansiriya Medical Journal · doi:10.4103/mj.mj_38_23 · Cited by 1 · see citing works
HIF-1α gene/protein and oxidative stress in patients with colorectal cancer: A pilot study
Akbar, S., Fazeli, M. S., Hemmati, R., Pirzadeh, M., Seyedan, S. M., Ferns, G. A., Pakzad, R., Yazdanian, Z., & Mobarra, N. (2023) · Gene Reports · doi:10.1016/j.genrep.2023.101783
Long-term Hypoxia Inhibits Sphere Formation on PC-3 and MDA-MB-231 Cell Line Models
Akhunzianov, A. A., Filina, J. V., Zolotykh, M. A., Rizvanov, A. A., & Рифкатовна, М. Р. (2024) · The Open Biochemistry Journal · doi:10.2174/011874091x307243240513092933
Role of the bone microenvironment in systemic breast cancer growth and metastasis
Aslan, Y. (2020) · theses.fr (ABES) · doi:10.70675/a6793073zd42dz4dacz843azd9606734d152
- Authors
- Wang, H. X., Qin, C., Han, F. Y., Wang, X. H., & Li, N.
- Affiliations
- Henan Medical University (CN)
- Venue
- Genetics and Molecular Research
- Publisher
- Genetics and Molecular Research
- Published
- 2014
- Volume
- 13
- Issue
- 2
- Pages
- 2817-2826
- ISSN
- 1676-5680 (ISSN-L)
- OpenAlex
- W2119138659
- Cited by
- 22
- References
- 24
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 2
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genetics and Molecular Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- HIF-2α, breast cancer, MMP-2, prognostic factors, tumor invasion, lymph node metastasis, distant metastasis, overall survival, tumor size, T stage, hypoxia
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Adult, Aged, Aged, 80 and over, Breast Neoplasms, Female, Humans, Lymph Nodes, Middle Aged, Prognosis, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Survival Rate, Disease Progression, Matrix Metalloproteinase 2, Basic Helix-Loop-Helix Proteins
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